The group A streptococci produce a large number of extracellular products, some of which may play a role in the pathogenesis of streptococcal infections and their sequelae. This proposal is addressed to a study of two of these products, streptolysin O (SLO) and streptolysin S (SLS). These cytolytic toxins have been investigated for many years, but the nature of their effects on the membranes of susceptible cells is not yet understood. Some investigators believe that SLO or SLS may play a role in the pathogenesis of rheumatic fever, and several recent studies have suggested that sublethal concentrations of these toxins affect certain host defense cell functions. A greater understanding of the effects of SLO and SLS on crucial membrane functions in mammalian cells would be useful in assessing the role of these toxins in streptococcal diseases. The effects of these two streptococcal toxins on membrane functions such as passive and active transport, pinocytosis, and phagocytosis, will be studied in established mammalian cell cultures, and in macrophages, an important host defense cell. The possibility that SLO or SLS affect the fluidity and fusion characteristics of membranes will be studied in BHK cells, using an enveloped virus as a probe of these properties. The effects of SLS on model membrane liposomes will be studied in an effort to determine the mechanism of action of this toxin on membrane phospholipids. The nature of the membrane structural alterations produced by SLO in erythrocyte membranes will be studied using freeze-etch procedures and the ability of toxin-treated erythrocyte membranes to reseal themselves will be examined in electronmicroscopy and biochemical studies.